Navigation Links
Blocking DNA repair protein could lead to targeted, safer cancer therapy
Date:6/1/2010

PITTSBURGH, June 1 Researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine have discovered that inhibiting a key molecule in a DNA repair pathway could provide the means to make cancer cells more sensitive to radiation therapy while protecting healthy cells.

The findings are published in Science Signaling and provide new insights into mechanisms of how the body fixes environmentally induced DNA damage and into the deadly neurological disease ataxia-telangiectasia (A-T), said senior author Christopher Bakkenist, Ph.D., assistant professor of radiation oncology, pharmacology and chemical biology at UPCI and the School of Medicine.

"A characteristic symptom of A-T is heightened sensitivity to ionizing radiation, such as X-rays and gamma rays," he said. "If we understand why that happens, then we might be able to reproduce it to make tumor cells vulnerable to radiation treatments while sparing healthy cells, which would make therapy more effective while minimizing side effects."

In A-T, brain areas that control movement progressively degenerate, causing walking and balance problems. Patients carry a gene mutation that stops production of a protein called ATM kinase, which spurs other proteins involved in normal cell division, DNA repair and cell death.

Radiation causes DNA mutations during the process of cell division, when genetic material is copied for a new cell to form. The cell has repair pathways that include checkpoints to look for errors as well as methods to repair them, but if enough mutations accumulate, the cell could become cancerous or self-destruct. A-T patients, who lack the kinase, have a higher risk for developing cancer, Dr. Bakkenist said.

He and his colleagues tested what would happen if they blocked the activity of ATM kinase in cells that make the protein. They had already determined that administering an ATM kinase inhibitor from 15 minutes to 75 minutes after radiation exposure was sufficient to make normal cells more sensitive to the effects of radiation.

To their surprise, they found that inactivation of ATM kinase prevented a type of DNA repair that is essential for proper duplication of genetic material during replication. However, A-T cells did not have this problem despite lacking the kinase; they presumably use another method to check for and correct those errors.

The discovery revealed a new approach to target cancer.

"A characteristic of tumor cells is that they rapidly replicate, possibly because they have mutations that encourage cell division or that thwart repair pathways," Dr. Bakkenist explained. "But ATM kinase remains present in the vast majority of human cancers, so that suggests it is needed by those diseased cells during replication."

Cells that, unlike cancer cells, are not going through what's known as replication stress, would not be affected by an ATM inhibitor and, like A-T cells, likely have another way of repairing certain radiation-induced mutations, he said.

"So that would make cancer cells particularly vulnerable to an ATM inhibitor, while healthy cells should be unaffected," Dr. Bakkenist said.

He and his team are now studying the effects of such inhibitors on pancreatic, lung and breast cancer cells.


'/>"/>

Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

Related medicine news :

1. Blocking Protein May Stem COPD
2. Notch-blocking drugs kill brain cancer stem cells, yet multiple therapies may be needed
3. Potential New Source of Stem Cells for Heart Repair
4. Research team documents benefits of endovascular stent repair for traumatic aortic injury
5. Study links microRNA to shut-down of DNA-repair genes
6. Stem cells from surgery leftovers could repair damaged hearts
7. Cedars-Sinai study examines regional use of minimally invasive repair of aneurysms
8. Stirling Dental Laboratory, Experts in Emergency Denture Repair Service, Gives Back to Community
9. Newly identified proteins critical to FA pathway DNA repair function
10. Minimally invasive sports hernia repair may get athletes back in the game faster, study says
11. Repair of torn knee meniscus at the time of ACL reconstruction is safe and effective for children
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/13/2016)... Coral Springs, FL (PRWEB) , ... February 13, 2016 , ... ... on the environmental impact of American businesses. , The increasingly modern world of ... rely more often on non-renewable energy sources such as oil and coal, which pollutes ...
(Date:2/13/2016)... Canada (PRWEB) , ... February 13, 2016 , ... In ... foot forward. They’ll groom themselves to perfection, go out of their way to be ... date – just take a look at any online dating profile. , A ...
(Date:2/12/2016)... ... February 12, 2016 , ... The law firm of Morrow, ... Parishes. The purpose of these scholarships is to encourage applicants to pursue a ... seek employment within these two parishes. , “We have available jobs in St. ...
(Date:2/12/2016)... Falls Church, VA (PRWEB) , ... February 12, ... ... in Store?, Feb. 29, 2016 — 1:30 p.m. – 3:00 p.m. EST, ... burner issue in the life cycle of pharmaceutical products, garnering increased attention from ...
(Date:2/12/2016)... ... February 12, 2016 , ... T.E.N., a technology and information ... ISE Southeast Awards 2016. Finalists and winners of the ISE® Awards for both ... and Awards Gala on March 15, 2016 at the Westin Peachtree Plaza, Atlanta. ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... 12, 2016  SI-BONE, Inc., a medical device company that pioneered ... minimally invasive surgical (MIS) device indicated for fusion for certain disorders ... (NGS), the Medicare Administrative Contractor (MAC) covering the states of ... Maine , Massachusetts , Minnesota ... York , Rhode Island , ...
(Date:2/12/2016)...  Memorial Hermann Health System has teamed up with ... bring a one-of-a-kind experience to pediatric patients at ... as 360-degree video and Google Cardboard, Howard was able ... giving the patients and their families an unexpected, and ... on video . Memorial Hermann IRONMAN ...
(Date:2/12/2016)... Feb. 12, 2016 On Thursday, Feb. 11, ... at St. David,s North Austin Medical Center successfully completed ... Xi ® Surgical System with Trumpf Medical,s ... Thiru Lakshman , M.D., colorectal surgeon at the ... utilizing Integrated Table Motion technology, which seamlessly combines the ...
Breaking Medicine Technology: